دورية أكاديمية
Il34 rescues metronidazole-induced impairment of spinal cord regeneration in zebrafish central nervous system.
العنوان: | Il34 rescues metronidazole-induced impairment of spinal cord regeneration in zebrafish central nervous system. |
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المؤلفون: | Liu JX; Division of Development Biology & Regenerative Medicine, South China University of Technology, Guangzhou 510006, China., Lai ST; Division of Development Biology & Regenerative Medicine, South China University of Technology, Guangzhou 510006, China., Bai J; Division of Development Biology & Regenerative Medicine, South China University of Technology, Guangzhou 510006, China., Xu J; Division of Development Biology & Regenerative Medicine, South China University of Technology, Guangzhou 510006, China. |
المصدر: | Yi chuan = Hereditas [Yi Chuan] 2024 Jun 20; Vol. 46 (6), pp. 478-489. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Ke xue chu ban she Country of Publication: China NLM ID: 9436478 Publication Model: Print Cited Medium: Print ISSN: 0253-9772 (Print) Linking ISSN: 02539772 NLM ISO Abbreviation: Yi Chuan Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Beijing : Ke xue chu ban she, |
مواضيع طبية MeSH: | Zebrafish* , Metronidazole*/pharmacology , Metronidazole*/adverse effects , Spinal Cord Regeneration*/drug effects , Spinal Cord Injuries*/metabolism, Animals ; Interleukins/genetics ; Interleukins/metabolism ; Central Nervous System/drug effects ; Central Nervous System/metabolism ; Zebrafish Proteins/genetics ; Zebrafish Proteins/metabolism ; Spinal Cord/drug effects ; Spinal Cord/metabolism |
مستخلص: | Metronidazole (MTZ), a commonly used anti-infective drug in clinical practice, has also been employed as a prodrug in cell-targeted ablation systems in scientific research, exhibiting significant application value. However, it has been demonstrated that MTZ can induce neurotoxic symptoms to some extent during its use, and there is currently a lack of effective means to circumvent its toxicity in both clinical and research settings, which limits its application. Therefore, exploring the specific mechanisms underlying MTZ-induced neurotoxic symptoms and elucidating countermeasures will enhance the practical value of MTZ. In this study, using a zebrafish spinal cord injury regeneration model, we confirmed that MTZ neurotoxicity leads to impaired axon regeneration in the central nervous system. By overexpressing il34 in the central nervous system of zebrafish, we eliminated the inhibitory effect of MTZ on axonal regeneration and demonstrated that the pro-regenerative effect against MTZ neurotoxicity is not caused by excessive macrophages/microglia chemoattracted by interleukin 34(Il34). Transcriptome sequencing analysis and GO enrichment analysis of differentially expressed genes between groups revealed that Il34 may counteract MTZ neurotoxicity and promote spinal cord injury repair through biological processes that enhance cellular adhesion and cell location. In summary, our work uncovers a possible cause of MTZ neurotoxicity and provides a new perspective for eliminating MTZ toxicity. |
فهرسة مساهمة: | Keywords: Il34; extracellular matrix (ECM); inflammation; macrophage/microglia; metronidazole (MTZ); neurotoxicity; spinal cord regeneration; zebrafish Local Abstract: [Publisher, Chinese] 甲硝唑(metronidazole,MTZ)是临床常用的抗感染药物,同时在科学研究中被用作细胞靶向消融系统的前体药物,具有极高的应用价值。但MTZ会引起一定程度的神经毒性症状,目前临床及科研使用过程中也缺乏规避其毒性的有效手段,这在一定程度上限制了其应用。因此,探究MTZ引起神经症状的具体机制并探讨应对措施将更大程度地发挥MTZ的实用价值。本研究利用斑马鱼( Danio rerio )脊髓损伤再生模型确认了MTZ的神经毒性导致斑马鱼中枢神经系统轴突再生障碍,通过在斑马鱼中枢神经系统中过表达 il34 消除了MTZ对轴突再生的抑制,并证明了这种抗MTZ神经毒性的促再生作用不是由白细胞介素34 (interleukin 34,Il34)趋化的过量巨噬细胞/小胶质细胞所介导。通过转录组测序分析组间差异表达基因的GO富集分析发现,Il34通过促进细胞间的黏附和细胞定位等生物学过程抗MTZ神经毒性从而促进脊髓损伤修复。综上所述,本研究揭示了MTZ神经毒性的可能原因,为消除MTZ毒性提供了一个新的视角。. |
المشرفين على المادة: | 140QMO216E (Metronidazole) 0 (Interleukins) 0 (Zebrafish Proteins) |
تواريخ الأحداث: | Date Created: 20240617 Date Completed: 20240617 Latest Revision: 20240703 |
رمز التحديث: | 20240704 |
DOI: | 10.16288/j.yczz.24-083 |
PMID: | 38886151 |
قاعدة البيانات: | MEDLINE |
تدمد: | 0253-9772 |
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DOI: | 10.16288/j.yczz.24-083 |